Document Detail


Thrombin peptide TP508 stimulates cellular events leading to angiogenesis, revascularization, and repair of dermal and musculoskeletal tissues.
MedLine Citation:
PMID:  17079379     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The thrombin peptide, TP508, also known as Chrysalin (OrthoLogic, Tempe, Arizona), is a twenty-three-amino-acid peptide that represents a portion of the receptor-binding domain of the native human thrombin molecule that has been identified as the binding site for a specific class of receptors on fibroblasts and other cells. Preclinical studies with this peptide have shown that it can accelerate tissue repair in both soft and hard tissues by mechanisms that appear to involve up-regulation of genes that initiate a cascade of healing events. These events include recruitment and activation of inflammatory cells, directed migration of cells (chemotaxis), cell proliferation, elaboration of extra-cellular matrix, and accelerated revascularization of the healing tissues. Early preclinical dermal wound-healing studies showed that TP508 accelerated healing of both incisional wounds and full-thickness excisional wounds in normal and ischemic skin. In all of these studies, the accelerated healing was associated with increased neovascularization across the incision or in the granulating wound bed. Studies in a rat fracture model have also shown that TP508 accelerates the rate of fracture repair. Gene array analysis of fracture callus from control and TP508-treated fractures indicated that TP508 treatment was associated with an up-regulation of early response elements, inflammatory mediators, and genes related to angiogenesis. Similar to what had been seen in dermal wounds, histology from rat fracture callus twenty-one days after treatment indicated that fractures treated with TP508 had significantly more large functional blood vessels than did fractures in the control animals. In vitro studies support these in vivo data and indicate that TP508 may have a direct angiogenic effect by promoting the rate of new vessel growth. The results from phase-1 and phase-2 human clinical studies have shown a positive stimulatory effect of TP508 in the healing of diabetic ulcers and in the repair of fractures to the distal aspect of the radius. Collectively, these studies suggest that TP508 accelerates tissue repair by initiating a cascade of events that lead to an increased rate of tissue revascularization and regeneration.
Authors:
James T Ryaby; Michael R Sheller; Benjamin P Levine; Dale G Bramlet; Amy L Ladd; Darrell H Carney
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  The Journal of bone and joint surgery. American volume     Volume:  88 Suppl 3     ISSN:  0021-9355     ISO Abbreviation:  J Bone Joint Surg Am     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-11-02     Completed Date:  2007-03-23     Revised Date:  2010-10-25    
Medline Journal Info:
Nlm Unique ID:  0014030     Medline TA:  J Bone Joint Surg Am     Country:  United States    
Other Details:
Languages:  eng     Pagination:  132-9     Citation Subset:  AIM; IM    
Affiliation:
OrthoLogic Corp, 1275 West Washington Street, Tempe, AZ 85281, USA. jryaby@olgc.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Diabetic Foot / drug therapy
Humans
Neovascularization, Physiologic / drug effects*
Peptide Fragments / pharmacology*,  therapeutic use
Radius Fractures / drug therapy
Rats
Thrombin / pharmacology*,  therapeutic use
Wound Healing / drug effects*
Chemical
Reg. No./Substance:
0/Peptide Fragments; 0/rusalatide acetate; EC 3.4.21.5/Thrombin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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